Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains

Abstract Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despi...

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Published in:Journal of neuropathology and experimental neurology Vol. 79; no. 8; pp. 902 - 907
Main Authors: Verheijen, Bert M, Morimoto, Satoru, Sasaki, Ryogen, Oyanagi, Kiyomitsu, Kokubo, Yasumasa, Kuzuhara, Shigeki, van Leeuwen, Fred W
Format: Journal Article
Language:English
Published: England Oxford University Press 01.08.2020
by American Association of Neuropathologists, Inc
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Amyotrophic Lateral Sclerosis - pathology
Brain - metabolism
Brain - pathology
Brain diseases
Brain research
Dementia
Development and progression
Endemic diseases
Frameshift Mutation
Gene mutations
Genetic aspects
Health aspects
Homeostasis
Humans
Japan
Parkinsonism
Protein metabolism disorders
Proteins
Proteostasis - genetics
Proteostasis Deficiencies - genetics
Proteostasis Deficiencies - metabolism
Proteostasis Deficiencies - pathology
Ubiquitin
Ubiquitin - genetics
Japan
Protein aggregation
UBB
Kii ALS/PDC
Protein quality control
Tauopathy
Ubiquitin-proteasome system
Autophagy
Unfolded protein response
UBB+1
ISSN:0022-3069, 1554-6578, 1554-6578
Online Access:Get full text
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Summary:Abstract Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.
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ISSN:0022-3069
1554-6578
1554-6578
DOI:10.1093/jnen/nlaa056